ミクログリア分化異常からみた精神神経疾患：患者由来iMG細胞を用いた橋渡し研究

抄録

Microglia have been highlighted to understand the underlying pathophysiology of various neuropsychiatric disorders. Postmortem brain analysis and PET imaging analysis are two major methods to estimate microglial activation in humans, however only a limited aspect of microglial activation can be measured by these methods. Dynamic analysis using fresh microglia in human brain is an ideal method, however technological and ethical considerations have limited the ability to conduct research using fresh brain microglia.

To overcome this limitation, we have originally developed a technique to create directly induced microglia-like (iMG) cells from fresh human peripheral blood monocytes adding GM-CSF and IL-34 for 2 weeks, instead of brain biopsy (Sci Rep 2014). Using the iMG cells, dynamic morphological and molecular-level analyses such as real-time cell differentiation, phagocytosis and cytokine releases are applicable.

We have used the iMG cells as surrogate cells of human brain microglia, and revealed previously-unknown dynamic pathophysiology of microglia in patients with Nasu-Hakola disease (Sci Rep 2014), fibromyalgia (Sci Rep 2017) and rapid-cycling bipolar disorder (Front Immunology 2017).

In addition, we have recently shown microglia-related pathophysiology using plasma such as human metabolome analysis focusing on the tryptophan-kynurenine pathway and neuron-related exosome analysis.

We believe that these indirect methods using human bloods shed new light on clarifying dynamic molecular pathologies of microglia in a variety of neuropsychiatric disorders.